Abstract
Objective To explore the effects of proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in acute leukemia cell line HEL. Methods Tumor cell growth inhibition and apoptosis was measured by MTF assay and FACS analysis, respectively. Apoptosis- and cell eycle-associatd protein expression levels were measured by Western blotting assay. Results Bortezomib induced the suppression of tumor cell growth and apoptosis in a dose-dependent manner with an inhibitor concentration ICso values 7.15 nmol/L in acute leukemia cell line HEL. Further combination treatment with doxorubicin or cytarabine increased tumor cell growth suppression in acute leukemia cell line, as compared to single drug treatment alone. Bortezomib caused an increase in G2/M in a time-dependent manner. Bortezomib alone and in combination with chemotherapeutic agents treatment increased the bax and p27 expression and decreased the bcl-2 expression even without influencing p53 expression levels. Conclusion Bortezomib may be an effective therapeutic drug for patients with acute leukemia. Combining bortezomib with doxorubiein might be more effeetive for displaying tumor cell growth inhibitor effects in acute leukemia cells through regulation of bcl-2, bax and P27 nroteins and indenendent of P53 status. Key words: Neoplasms, experimental; Bortezomib; Leukemia, acute; Apoptosis
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